This study was carried out on the trial to examine the utility of interleukin-18 (IL-18) for cancer immunotherapy. Recent development of immune checkpoint inhibitors targeting PD-1 or PD-L1 for cancer immunotherapy have made a breakthrough and opened new era in cancer therapy. This therapy requires further progress in augmentation of efficacy and suppression of adverse events. Using an animal model of cancer peritoneal dissemination, we demonstrated that IL-18 markedly augments the efficacy of immune checkpoint inhibitors suppressing tumor growth and prolonging survival of mice inoculated with tumor cells. As a mechanism, it was considered that IL-18 strongly enhances expansion of effector cells including NK cells, γδ T cells, and CD8+ T cells, and oppositely suppresses Treg cells. These results demonstrated utility of IL-18 in cancer immunotherapy and suggested usage of IL-18 for wider range of immunotherapy.